The Romano-African Domus: studies in space, decoration, and function

The introduction (chapter I) will present the topic of the present research in two paragraphs. The one will discuss the problems relating to the study of domestic art in Roman Africa and the approach of scholars to them in order to highlight the new aspect of this research. The second one will describe the methodology that will be used in the study of the relationship between architectural forms and mosaic decoration of African domestic architecture during the high and late Empire (Maps 1-2). The following chapters will describe eight room-types in term of architectural layout and mosaic decoration. By following the imaginary route of an ancient guest visiting the Romano-African house, the analysis will begin with the description of the spaces of higher accessibility: the vestibulum as the point of transition from outside and inside and its annexed spaces such as audience-chamber, cella ianitoris, and room for storing sportulae (chapter 2); and the peristyle as a passageway to rooms arranged around it (chapter 3). The analysis of the peristyle as an open space will be followed by the study of the secondary courtyard in chapter 4. The discussion will continue with the description of the reception rooms as public spaces where the house-owner received his selected guests: main triclinium (chapter 5), secondary triclinium (chapter 6), and assembly-rooms (chapter 7). The analysis will end with the description of the most private parts of the house: the cubiculum as the room of a more selective admission (chapter 8) and the private apartments as the spaces reserved for the members of the master's family (chapter 9). Conclusions will follow in chapter 10. The whole analysis will be carried out with the support of the catalogue listing the main Romano-African houses

The Romano-African Domus: studies in space, decoration, and function

The introduction (chapter I) will present the topic of the present research in two paragraphs. The one will discuss the problems relating to the study of domestic art in Roman Africa and the approach of scholars to them in order to highlight the new aspect of this research. The second one will describe the methodology that will be used in the study of the relationship between architectural forms and mosaic decoration of African domestic architecture during the high and late Empire (Maps 1-2). The following chapters will describe eight room-types in term of architectural layout and mosaic decoration. By following the imaginary route of an ancient guest visiting the Romano-African house, the analysis will begin with the description of the spaces of higher accessibility: the vestibulum as the point of transition from outside and inside and its annexed spaces such as audience-chamber, cella ianitoris, and room for storing sportulae (chapter 2); and the peristyle as a passageway to rooms arranged around it (chapter 3). The analysis of the peristyle as an open space will be followed by the study of the secondary courtyard in chapter 4. The discussion will continue with the description of the reception rooms as public spaces where the house-owner received his selected guests: main triclinium (chapter 5), secondary triclinium (chapter 6), and assembly-rooms (chapter 7). The analysis will end with the description of the most private parts of the house: the cubiculum as the room of a more selective admission (chapter 8) and the private apartments as the spaces reserved for the members of the master's family (chapter 9). Conclusions will follow in chapter 10. The whole analysis will be carried out with the support of the catalogue listing the main Romano-African houses

Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multi-centre, randomised, phase II trial (RT3VIN)

Objective To compare the recurrence rates after complete response to topical treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia (VIN) 3. Design A prospective, open, randomised multicentre trial. Setting 32 general hospitals located in Wales and England. Population or Sample 180 patients were randomised consecutively between 21 October 2009 and 11 January 2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to imiquimod (of whom 42 completely responded to treatment). Methods After 24 weeks of treatment, complete responders were followed up at 6‐monthly intervals for 24 months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was assessed and any new lesions were biopsied for histology. Main outcome measures Time to histologically confirmed disease recurrence (any grade of VIN). Results The median length of follow up was 18.4 months. At 18 months, more participants were VIN‐free in the cidofovir arm: 94% (95% CI 78.2–98.5) versus 71.6% (95% CI 52.0–84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95–12.60, P = 0.059; multivariable HR 3.53, 95% CI 0.96–12.98, P = 0.057). The number of grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus cidofovir: 27/41 (66%), χ2 = 0.665, P = 0.415), with no grade 4+. Conclusions Long‐term data indicates a trend towards response being maintained for longer following treatment with cidofovir than with imiquimod, with similar low rates of adverse events for each drug. Adverse event rates indicated acceptable safety of both drugs Tweetable abstract Long‐term follow up in the RT3VIN trial suggests cidofovir may maintain response for longer than imiquimod

Fulvestrant plus vandetanib versus placebo for the treatment of patients with metastatic breast cancer resistant to aromatase inhibitor therapy (FURVA): a multicentre, Phase 2, randomised controlled trial

Background: FURVA, a randomised, double-blind Phase II trial, investigated whether the addition of vandetanib to fulvestrant improved progression-free survival (PFS) in patients with an aromatase inhibitor(AI)-resistant advanced breast cancer. Methods: Postmenopausal women with oestrogen receptor-positive (ER+ve)/HER2-negative advanced breast cancer, who experienced disease progression on an AI, were randomised (1:1) to fulvestrant 500 mg (Q28) with vandetanib 300 mg od (f + v) or placebo (f + p) until disease progression or discontinuation. The primary endpoint was PFS; secondary endpoints included overall survival (OS) and the influence of REarranged during Transfection (RET) signalling on outcomes. Results: In total, 165 participants were randomised to f + v (n = 80) or f + p (n = 85). Median PFS was 5.5 months (m) for f + v compared to 5.5 m for f + p (hazard ratio (HR) 0.88; 95% CI: 0.62–1.23; P = 0.22). Unexpectedly, high total RET expression was associated with a PFS advantage of 8.87 m vs 3.94 with low RET (HR 0.493: 95% CI 0.32–0.77; P = 0.002) independent of the treatment arm, supported by an OS advantage 21.95 m vs 18.04 (HR 0.584; 95% CI 0.34–1.00; P = 0.051) in the high-RET group. Conclusion: The addition of vandetanib to fulvestrant does not improve PFS. However, high total RET expression was associated with improved PFS, suggesting RET may have a prognostic role in patients treated with fulvestrant. Clinical trial registration: ClinicalTrials.gov, NCT02530411

The VALTIVE1 study protocol: a study for the validation of Tie2 as the first tumour vascular response biomarker for VEGF inhibitors

Background: Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.56. The aim of the VALTIVE1 study is to validate the utility of plasma Tie2 as a vascular response biomarker and to optimise the Tie2-definition of vascular response so that the subsequent randomised discontinuation VALTIVE2 study can be powered optimally. Methods: VALTIVE1 is a multi-centre, single arm, non-interventional biomarker study, with a sample size of 205 participants (176 bevacizumab-treated participants + 29 participants receiving bevacizumab and olaparib/PARPi), who are 16 years or older, have FIGO stage IIIc/IV ovarian cancer on treatment with first-line platinum-based chemotherapy and bevacizumab. Their blood plasma samples will be collected before, during, and after treatment and the concentration of Tie2 will be determined. The primary objective is to define the PFS difference between Tie2-defined vascular responders and Tie2-defined vascular non-responders in patients receiving bevacizumab for high-risk Ovarian Cancer. Secondary objectives include defining the relationship between Tie2-defined vascular progression and disease progression assessed according to RECIST 1.1 criteria and assessing the impact of PARPi on the plasma concentration of Tie2 and, therefore, the decision-making utility of Tie2 as a vascular response biomarker for bevacizumab during combined bevacizumab-PARPi maintenance. Discussion: There is an urgent need to establish a test that tells patients and their doctors when VEGFi are working and when they stop working. The data generated from this study will be used to design a second trial aiming to prove conclusively the value of the Tie2 test. Trial registration: ClinicalTrials.gov identifier: NCT04523116. Registered on 21 Aug 2020

BI06 Short sharp shock or slow burn: clinician perspectives on treatment of actinic keratoses with 5-fluorouracil 5% cream monotherapy vs. 5-fluorouracil/calcipotriol ointment combination therapy

Actinic keratoses (AK) are common in immunocompromised patients and associated with increased risk of cutaneous squamous cell carcinoma (cSCC). The current standard of care is 5-fluorouracil cream 5% (5-FU) monotherapy for 4 weeks. In recent years, 5-FU cream and calcipotriol ointment (5-FU-Cal) combination AK therapy for 4–6 days has emerged as potentially more effective and better tolerated, although the original randomized controlled trial (RCT) excluded immunosuppressed patients. Previously, we shared immunosuppressed patients’ real-world perspectives of using 5-FU monotherapy vs. 5-FU-Cal combination therapy (Junejo MH, Demirel S, Matin R et al. Short shock or slow burn? Patient perspectives on treatment of actinic keratoses with 5-fluorouracil 5% cream monotherapy versus 5-fluorouracil plus calcipotriol combination therapy. Clin Exp Dermatol 2023; 48:31–2). The majority (81%) found 5-FU-Cal to be more effective than 5-FU monotherapy. Despite 47% reporting worse local skin reactions (LSRs), most preferred the 5-FU-Cal combination. We now report results from a clinician survey on the use of 5-FU monotherapy vs. 5-FU-Cal combination therapy for the treatment of AK. An online survey was sent to 200 UK consultant dermatologists. Fifty-seven (28.5%) completed the survey, all of whom reported using 5-FU monotherapy for treating AK in patients with prior cSCC; 43 (75%) reported this to be their preferred treatment. Most clinicians (n = 40; 70%) were aware of 5-FU-Cal combination therapy, although only 24 (42%) reported using it to treat AK in patients with prior cSCC. Of these, 18 (75%) used combination treatment for AK as part of field change, 14 (58%) used it for the treatment of patches of more than five AK and 13 (54%) used it for grouped AK. Very few (n = 4; 17%) used combination therapy for treatment of cSCC in situ (n = 4), single AK (n = 3) or superficial basal cell carcinoma (n = 1). Of 24 clinicians using 5-FU-Cal, the majority felt that patients developed LSRs often (n = 11; 46%) or always (n = 7; 29%); fewer felt that LSRs occurred sometimes (n = 5; 21%) or rarely (n = 1; 4%). Clinicians using combination therapy primarily felt the LSRs were moderate but not severe enough to require supplementary treatment or discontinuation (n = 17; 71%). Half (n = 12; 50%) of those using combination therapy felt patients did not signal a preference between 5-FU monotherapy vs. 5-FU-Cal combination therapy. Two-thirds (n = 38/57; 67%) of clinicians reported an interest in participating in a RCT comparing 5-FU vs. 5-FU-Cal vs. sunscreen alone for the treatment of AK in patients with prior cSCC. This is the first evaluation of clinician perspectives on the use of the newly emerging 5-FU-Cal therapy for AK. These data provide a rationale for the inclusion of combination 5-FU-Cal therapy in future studies using topical AK treatments for cSCC prevention in the UK

Gut Microbiome Modulation for Preventing and Treating Pediatric Food Allergies

The increasing prevalence and severity of pediatric food allergies (FA) demands innovative preventive and therapeutic strategies. Emerging evidence suggests a pivotal role for the gut microbiome in modulating susceptibility to FA. Studies have demonstrated that alteration of gut microbiome could precede FA, and that particular microbial community structures early in life could influence also the disease course. The identification of gut microbiome features in pediatric FA patients is driving new prevention and treatment approaches. This review is focused on the potential role of the gut microbiome as a target for FA prevention and treatment